POS0077 SEX DIFFERENCES IN EFFECTIVENESS OF FIRST-LINE TUMOR NECROSIS FACTOR INHIBITORS IN PSORIATIC ARTHRITIS; RESULTS FROM THIRTEEN COUNTRIES IN THE EuroSpA RESEARCH COLLABORATION NETWORK
Authors: P. Hellamand, M. G. H. Van de Sande, L. Midtbøll Ørnbjerg, T. Klausch, N. Trokovic, T. Sokka-Isler, M. J. Santos, E. Vieira-Sousa, A. G. Loft, B. Glintborg, M. Østergaard, U. Lindström, J. K. Wallman, B. Michelsen, B. Moeller, R. Micheroli, C. Codreanu, C. Mogosan, K. Laas, Z. Rotar, K. M. Fagerli, M. Tomsic, I. Castrejon, M. Pombo-Suarez, B. Gudbjornsson, T. Love, K. Pavelka, J. Zavada, G. Kenar, H. Yarkan-Tuğsal, M. L. Hetland, I. Van der Horst-Bruinsma
Journal: Annals of the Rheumatic Diseases (2022)

Background Evidence demonstrates sex differences in disease presentation, physical function, treatment response and drug retention in patients with psoriatic arthritis (PsA). Data from observational cohort studies indicate female sex is associated with reduced effectiveness of tumor necrosis factor inhibitors (TNFis) 1,2 . Although, conflicting results are also reported 3,4 . We sought to validate prior studies using data from a large multinational cohort based on real-life clinical practice. Objectives To investigate sex differences in treatment response and drug retention rates in clinical practice among patients with PsA, treated with their first TNFi. Methods Data from biologic-naïve PsA patients initiating a TNFi in the EuroSpA registries were pooled. In the primary analysis, propensity-score weighting was applied to assess the causal effect of sex on low disease activity (LDA) according to DAS28-CRP at 6 months. A generalized linear regression model was used to estimate the causal risk difference (RD) and relative risk (RR) of sex on LDA. Possible covariates influencing the outcome were determined a priori and selected based on availability in the database (&lt;20% missing). The final covariates included were country, age, conventional synthetic disease-modifying antirheumatic drug use at baseline and TNFi start year. In the secondary analysis, drug retention was assessed over 24 months of follow-up by Kaplan-Meier curves and log-rank test. Results In total, 7,679 PsA patients with available data on DAS28-CRP at 6 months were assessed for treatment response. Baseline characteristics are shown in the Table 1. In the adjusted analysis, the probability for females to have LDA was 17% (RR, 0.83; 95% confidence interval [CI], 0.81 to 0.85) lower compared to males and the difference in probability for having LDA was 13 percentage points (RD, 0.13; 95% CI, 0.11 to 0.15). The survival analysis included 18,599 PsA patients with available data on retention rates. The TNFi 6/12/24-month retention rates were significantly lower in females (81%/68%/56%) compared to males (89%/80%/69%), see Figure 1. Table 1. Baseline characteristics of all biologic-naïve PsA patients treated with their first TNFi and available DAS28-CRP at 6 month, data pooled across all countries Female Male Mean (SD), median [IQR] or percentages Mean (SD), median [IQR] or percentages Age (years) 49.7 (12.5) 47.8 (11.9) Disease duration (years) 4.0 [1.0, 10.0] 4.0 [1.0, 10.0] TNFi start year 1999-2009 29% 29% 2010-2013 26% 27% 2014-2016 25% 24% 2017-2020 20% 20% Concomittant csDMARD 75% 77% DAS28-CRP 4.4 (1.2) 4.2 (1.2) DAPSA28 32 (16) 29 (16) CRP (mg/L) 7.0 [3.0, 17.0] 8.0 [3.3, 19.0] SJC (0-28) 3.0 [1.0, 6.0] 3.0 [1.0, 6.0] TJC (0-28) 6.0 [2.0, 10.0] 4.0 [2.0, 9.0] VAS pain, mm 61 (23) 55 (23) VAS fatigue, mm 62 (26) 53 (27) Data are as observed, mean (SD), median [IQR] or percentage. TNFi, tumor necrosis factor inhibitor; csDMARD, Conventional synthetic disease-modifying antirheumatic drugs; DAS28-CRP, Disease Activity Score 28-joint count C reactive protein; DAPSA28, Disease Activity in PsA 28; CRP, C-reactive protein; SJC, swollen joint count; TJC, tender joint count. Conclusion Treatment efficacy and retention rates are lower among female patients with PsA initiating their first TNFi. Females presented with higher 28-tender joint count and higher scores on patient reported outcomes at baseline, reflecting differences in disease expression. Recognizing these sex differences is of relevance for customized patient care and may improve patient education. References [1]Højgaard, et al. Rheumatology (Oxford). 2018 Sep 1;57(9):1651-1660. [2]Vieira-Sousa, et al. J Rheumatol. 2020 May 1;47(5):690-700. [3]Kristensen, et al. Ann Rheum. Dis. 2008 Mar;67(3):364-9. [4]Iervolino, et al. J Rheumatol. 2012 Mar;39(3):568-73. Acknowledgements Novartis Pharma AG and IQVIA for supporting the EuroSpA collaboration. Disclosure of Interests Pasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: UCB, Consultant of: Abbvie, Eli Lily, Novartis, UCB, Grant/research support from: Novartis, Janssen, UCB and Eli Lilly, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Thomas Klausch: None declared, Nina Trokovic: None declared, Tuulikki Sokka-Isler Consultant of: Abbvie, Amgen, BMS, Celgene, DiaGraphIT, Medac, MSD, Novartis, Orionpharma, Pfizer, Roche, Sandoz, and UCB, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis and Pfizer, Elsa Vieira-Sousa Speakers bureau: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Consultant of: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Grant/research support from: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie, BMS, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene, Novartis, Ulf Lindström: None declared, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly and Novartis, Brigitte Michelsen Grant/research support from: Novartis, Burkhard Moeller Speakers bureau: MSD, Synergy, Eli Lilly, Bristol-Myers-Squibb, Janssen-Cilag, AbbVie and Pfizer, Raphael Micheroli: None declared, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Corina Mogosan Speakers bureau: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Karin Laas Speakers bureau: Amgen, Janssen, Novartis and Abbvie, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Karen Minde Fagerli: None declared, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Isabel Castrejon Speakers bureau: Lilly, BMS, Janssen, MSD and Abbvie, Consultant of: Lilly, BMS, Janssen, MSD and Abbvie, Manuel Pombo-Suarez Consultant of: Abbvie, MSD and Roche, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Consultant of: Amgen and Novartis, Thorvardur Love: None declared, Karel Pavelka Speakers bureau: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche and AbbVie, Consultant of: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche and AbbVie, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis and UCB, Consultant of: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis and UCB, Gökçe Kenar: None declared, Handan Yarkan-Tuğsal: None declared, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer and MSD, Consultant of: Abbvie, UCB, MSD, Novartis and Lilly, Grant/research support from: MSD, Pfizer, AbbVie and UCB